chr16-83968721-C-A

Variant names:

• chr16-83968721-C-A
• NM_019065.3:c.73C>A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_019065.3(NECAB2):​c.73C>A​(p.Arg25Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000228 in 877,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: NECAB2 NM_019065.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608

Genes affected

NECAB2 (HGNC:23746): (N-terminal EF-hand calcium binding protein 2) The protein encoded by this gene is a neuronal calcium-binding protein that binds to and modulates the function of at least two receptors, adenosine A(2A) receptor and metabotropic glutamate receptor type 5. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP7: Synonymous conserved (PhyloP=-0.608 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECAB2	NM_019065.3	c.73C>A	p.Arg25Arg	synonymous_variant	Exon 1 of 13	ENST00000305202.9	NP_061938.2
NECAB2	NM_001329748.1	c.73C>A	p.Arg25Arg	synonymous_variant	Exon 1 of 12		NP_001316677.1
NECAB2	NM_001329749.2	c.-151C>A		5_prime_UTR_variant	Exon 1 of 12		NP_001316678.1
NECAB2	XM_047434240.1	c.-22-3430C>A		intron_variant	Intron 1 of 11		XP_047290196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECAB2	ENST00000305202.9	c.73C>A	p.Arg25Arg	synonymous_variant	Exon 1 of 13	1	NM_019065.3	ENSP00000307449.4
NECAB2	ENST00000681513.1	n.478C>A		non_coding_transcript_exon_variant	Exon 1 of 13

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000228 AC: 2 AN: 877214 Hom.: 0 Cov.: 30 AF XY: 0.00000244 AC XY: 1 AN XY: 409082

Gnomad4 AFR exome AF: 0.0000599

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	12
DANN	Benign	0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-84002326;